A Total Diet Replacement Weight Management Program for Difficult-to-Treat Asthma Associated With Obesity

BackgroundObesity often is associated with uncontrolled, difficult-to-treat asthma and increased morbidity and mortality. Previous studies suggest that weight loss may improve asthma outcomes, but with heterogenous asthma populations studied and unclear consensus on the optimal method of weight management. The Counterweight-Plus Programme (CWP) for weight management is an evidence-based, dietitian-led total diet replacement (TDR) program.Research QuestionCan use of the CWP compared with usual care (UC) improve asthma control and quality of life in patients with difficult-to-treat asthma and obesity?Study Design and MethodsWe conducted a 1:1 (CWP to UC) randomized, controlled single-center trial in adults with difficult-to-treat asthma and BMI of ≥ 30 kg/m2. The CWP was a 12-week TDR phase (800 kcal/d low-energy formula) with stepwise food reintroduction and weight loss maintenance for up to 1 year. The primary outcome was the change in Asthma Control Questionnaire 6 (ACQ6) score over 16 weeks. The secondary outcome was change in Asthma Quality of Life Questionnaire (AQLQ) score.ResultsThirty-five participants were randomized (36 screened) and 33 attended the 16-week follow-up (n = 17 in the CWP group, n = 16 in the UC group). Overall, mean ACQ6 score at baseline was 2.8 (95% CI, 2.4-3.1). Weight loss was greater in the CWP than UC group (mean difference, –12.1 kg; 95% CI, –16.9 to –7.4; P < .001). ACQ6 score improved more in the CWP than UC group (mean difference, –0.69; 95% CI, –1.37 to –0.01; P = .048). A larger proportion of participants achieved the minimal clinically important difference in ACQ6 score with CWP than with UC (53% vs 19%; P = .041; NNT, 3 [95% CI, 1.5-26.9]). AQLQ score improvement was greater in the CWP than UC group (mean difference, 0.76; 95% CI, 0.18-1.34; P = .013).InterpretationUsing a structured weight management program results in clinically important improvements in asthma control and quality of life over 16 weeks compared with UC in adults with difficult-to-treat asthma and obesity. This generalizable program is easy to deliver for this challenging phenotype. Longer-term outcomes continue to be studied.Trial RegistryClinicalTrials.gov; No.: NCT03858608; URL: www.clinicaltrials.gov Obesity often is associated with uncontrolled, difficult-to-treat asthma and increased morbidity and mortality. Previous studies suggest that weight loss may improve asthma outcomes, but with heterogenous asthma populations studied and unclear consensus on the optimal method of weight management. The Counterweight-Plus Programme (CWP) for weight management is an evidence-based, dietitian-led total diet replacement (TDR) program. Can use of the CWP compared with usual care (UC) improve asthma control and quality of life in patients with difficult-to-treat asthma and obesity? We conducted a 1:1 (CWP to UC) randomized, controlled single-center trial in adults with difficult-to-treat asthma and BMI of ≥ 30 kg/m2. The CWP was a 12-week TDR phase (800 kcal/d low-energy formula) with stepwise food reintroduction and weight loss maintenance for up to 1 year. The primary outcome was the change in Asthma Control Questionnaire 6 (ACQ6) score over 16 weeks. The secondary outcome was change in Asthma Quality of Life Questionnaire (AQLQ) score. Thirty-five participants were randomized (36 screened) and 33 attended the 16-week follow-up (n = 17 in the CWP group, n = 16 in the UC group). Overall, mean ACQ6 score at baseline was 2.8 (95% CI, 2.4-3.1). Weight loss was greater in the CWP than UC group (mean difference, –12.1 kg; 95% CI, –16.9 to –7.4; P < .001). ACQ6 score improved more in the CWP than UC group (mean difference, –0.69; 95% CI, –1.37 to –0.01; P = .048). A larger proportion of participants achieved the minimal clinically important difference in ACQ6 score with CWP than with UC (53% vs 19%; P = .041; NNT, 3 [95% CI, 1.5-26.9]). AQLQ score improvement was greater in the CWP than UC group (mean difference, 0.76; 95% CI, 0.18-1.34; P = .013). Using a structured weight management program results in clinically important improvements in asthma control and quality of life over 16 weeks compared with UC in adults with difficult-to-treat asthma and obesity. This generalizable program is easy to deliver for this challenging phenotype. Longer-term outcomes continue to be studied. ClinicalTrials.gov; No.: NCT03858608; URL: www.clinicaltrials.gov Take-home PointsStudy Question: Can use of the Counterweight-Plus Programme (CWP) for weight management improve asthma control and quality of life in patients with difficult-to-treat asthma and obesity, compared with those receiving usual care (UC)?Results: Over 16 weeks, the CWP resulted in clinically relevant improvements in both asthma control and quality-of-life indexes, with substantial weight loss, as compared with UC.Interpretation: Initial results using the CWP are encouraging, and adherence to the program was better than expected, although longer-term outcomes are awaited to assess sustainability of the benefits seen. Study Question: Can use of the Counterweight-Plus Programme (CWP) for weight management improve asthma control and quality of life in patients with difficult-to-treat asthma and obesity, compared with those receiving usual care (UC)? Results: Over 16 weeks, the CWP resulted in clinically relevant improvements in both asthma control and quality-of-life indexes, with substantial weight loss, as compared with UC. Interpretation: Initial results using the CWP are encouraging, and adherence to the program was better than expected, although longer-term outcomes are awaited to assess sustainability of the benefits seen. Approximately 17% of people living with asthma have difficult-to-treat disease because of factors including poor inhaler technique, treatment nonadherence, and comorbidities such as obesity.1Global Initiative for AsthmaDiagnosis and management of difficult-to-treat and severe asthma. 2021. 23/05/2022. Global Initiative for Asthma website.www.ginasthma.org/severeasthmaGoogle Scholar,2Global Burden of Disease 2015 Chronic Respiratory Disease CollaboratorsGlobal, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015.Lancet Respir Med. 2017; 5: 691-706Abstract Full Text Full Text PDF PubMed Scopus (1361) Google Scholar Asthma associated with obesity is less steroid responsive; is linked with poorer control, quality of life, and increased morbidity and mortality; and has limited treatment options.3Sutherland E.R. Goleva E. Strand M. et al.Body mass and glucocorticoid response in asthma.Am J Respir Crit Care Med. 2008; 178: 682-687Crossref PubMed Scopus (254) Google Scholar,4Taylor B. Mannino D. Brown C. et al.Body mass index and asthma severity in the National Asthma Survey.Thorax. 2008; 63: 14-20Crossref PubMed Scopus (236) Google Scholar The pathophysiologic effects of obesity on asthma are multifactorial. Weight excess has direct effects on thoracic wall mechanics,5Jones R.L. Nzekwu M.M. The effects of body mass index on lung volumes.Chest. 2006; 130: 827-833Abstract Full Text Full Text PDF PubMed Scopus (646) Google Scholar as well as increased airway closure,6Kaminsky D.A. Chapman D.G. Holbrook J.T. et al.Older age and obesity are associated with increased airway closure in response to methacholine in patients with asthma.Respirology. 2019; 24: 638-645Crossref PubMed Scopus (14) Google Scholar,7Peters U. Subramanian M. Chapman D.G. et al.BMI but not central obesity predisposes to airway closure during bronchoconstriction.Respirology. 2019; 24: 543-550Crossref PubMed Scopus (21) Google Scholar airway hyperresponsiveness,8Orfanos S. Jude J. Deeney B.T. et al.Obesity increases airway smooth muscle responses to contractile agonists.Am J Physiol Lung Cell Mol Physiol. 2018; 315: L673-L681Crossref Scopus (34) Google Scholar,9Pampuch A. Milewski R. Rogowska A. et al.Predictors of airway hyperreactivity in house dust mite allergic patients.Adv Respir Med. 2019; 87: 152-158Crossref Scopus (3) Google Scholar and airway inflammation.10Kwon H. Pessin J.E. Adipokines mediate inflammation and insulin resistance.Front Endocrinol (Lausanne). 2013; 4: 71Crossref PubMed Scopus (402) Google Scholar, 11Pereira S A.-L.J. Adipokines: biological functions and metabolically healthy obese profile. J.Receptor Ligand Channel Res. 2014; 7: 15-25Crossref Scopus (17) Google Scholar, 12White S.R. Laxman B. Naureckas E.T. et al.Evidence for an IL-6-high asthma phenotype in asthmatic patients of African ancestry.J Allergy Clin Immunol. 2019; 144: 304-306.e4Abstract Full Text Full Text PDF Google Scholar A Cochrane review13Adeniyi F.B. Young T. Weight loss interventions for chronic asthma.Cochrane Database Syst Rev. 2012; 7: Cd009339PubMed Google Scholar of four studies (N = 197) suggested that weight loss may improve asthma control, but the quality of the evidence was poor and further well-constructed randomized controlled trials were recommended. In the United Kingdom, the Counterweight-Plus Programme (CWP) for weight management is a commercially available dietitian-supported regimen of total diet replacement (TDR), stepwise food reintroduction, and weight loss maintenance. It has shown efficacy in obesity (mean weight loss, 10 kg; approximately one-third achieving loss of ≥ 15 kg) and type 2 diabetes mellitus (remission in 46% of patients).14Lean M. Brosnahan N. McLoone P. et al.Feasibility and indicative results from a 12-month low-energy liquid diet treatment and maintenance programme for severe obesity.Br J Gen Pract. 2013; 63: e115-e124Crossref Scopus (57) Google Scholar,15Lean M.E. Leslie W.S. Barnes A.C. et al.Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial.Lancet. 2018; 391: 541-551Abstract Full Text Full Text PDF PubMed Scopus (868) Google Scholar Its effects on asthma have not been evaluated, and we hypothesized that use of the CWP would result in improvements in asthma control and asthma-related quality of life. To test this hypothesis, we performed a randomized, controlled, proof-of-concept feasibility trial of CWP in patients with obesity and difficult-to-treat asthma. Herein, we report the primary outcome results for the first 16 weeks of treatment after completion of the first phase of the intervention program. In this randomized, controlled, open-label, parallel study of a TDR weight loss program compared with usual care (UC) in individuals with difficult-to-treat asthma and obesity, participants were randomized 1:1 using a password-protected, online, third-party randomization service to CWP or UC.16Sealed Envelope. Simple randomisation service. 2021. Sealed Envelope website.https://www.sealedenvelope.com/simple-randomiser/v1/Google Scholar Study visits were scheduled at baseline and 16 weeks, with further visits planned for the 1-year and 2-year follow-up. The trial was approved by the West of Scotland Regional Ethics Committee (Identifier: 18/WS/0216), was sponsored and funded by an NHS Greater Glasgow and Clyde Endowment Fund, and is registered at ClinicalTrials.gov (Identifier: NCT03858608), where trial protocol is described.17National Institutes of Health Clinical CenterWeight loss for uncontrolled asthma associated with elevated BMI. NCT03858608. National Institutes of Health; 2022. 23/05/2022.https://ClinicalTrials.gov/show/NCT03858608Google Scholar The funder and contributors to the fund had no input in study design or the trial outcomes. Because of the COVID-19 pandemic, face-to-face follow-up study visits were substituted for telephone consultations where necessary to optimize data collection. Recruitment and randomization was undertaken by the clinical research fellow. Study visits and data collection were performed by the clinical research fellow and clinical research nursing team at the Glasgow Royal Infirmary Clinical Research Facility. Eligible participants 18 to 75 years of age with BMI of ≥ 30.0 kg/m2, a diagnosis of asthma according to Global Initiative for Asthma guidelines,18Global Initiative for AsthmaGlobal strategy for asthma management and prevention. 2015. 23/05/2022. Global Initiative for Asthma website.www.ginasthma.orgGoogle Scholar and difficult-to-treat disease according to Scottish Intercollegiate Guidelines Network/British Thoracic Society guidelines19British Thoracic Society and Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma. A national clinical guideline. 2014. 23/05/2022. British Thoracic Society website.https://www.brit-thoracic.org.uk/quality-improvement/guidelines/asthma/Google Scholar were identified from secondary and tertiary asthma clinics and ward admissions across NHS Greater Glasgow and Clyde (e-Appendix 1). Asthma clinicians and asthma specialist nurses referred patients to the clinical research fellow for screening after a brief explanation of the program. Asthma clinicians were aware of participation in the trial (consent forms were uploaded to electronic patient health-care records), but were not involved in recruitment, study visits, or data analysis. Eligible participants were provided with written information and were invited to attend the Glasgow Royal Infirmary Clinical Research Facility, where written informed consent was obtained before randomization and baseline data collection (visit 1). Participants were enrolled and randomized by the clinical research fellow. Baseline demographics, asthma and other medical history, and medication information were obtained at visit 1. At all visits, the Asthma Control Questionnaire 6 (ACQ6) and Asthma Quality of Life Questionnaire (AQLQ) scores were recorded. The ACQ6 is a validated asthma control score comprising six questions,20Juniper E.F. Byrne P.M. Guyatt G.H. et al.Development and validation of a questionnaire to measure asthma control.Eur Respir J. 1999; 14: 902Crossref PubMed Scopus (1813) Google Scholar a score of ≥ 1.5 reflecting poor disease control, and with a minimal clinically important difference (MCID) of 0.5. The AQLQ is a validated score comprising 32 questions covering several domains (symptoms, activity limitation, emotional function, and environmental stimuli) assessing quality of life in asthma.21Juniper E.F. Guyatt G.H. Willan A. et al.Determining a minimal important change in a disease-specific Quality of Life Questionnaire.J Clin Epidemiol. 1994; 47: 81-87Abstract Full Text PDF PubMed Scopus (1549) Google Scholar A higher score reflects better quality of life and the MCID is 0.5. At all visits, other data collected included anthropomorphic measures, health-care use, Medical Research Council dyspnea scale score, Hospital Anxiety Depression scale score, blood sampling, spirometry (Vitalograph ALPHA spirometer) as per European Respiratory Society/American Thoracic Society standards,22Miller M.R. Hankinson J. Brusasco V. et al.Standardisation of spirometry.Eur Respir J. 2005; 26: 319-338Crossref PubMed Scopus (11392) Google Scholar peak expiratory flow rate, fractional exhaled nitric oxide (Feno; NIOX VERO; Aerocrine AB) according to American Thoracic Society guidelines,23Dweik R.A. Boggs P.B. Erzurum S.C. et al.An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications.Am J Respir Crit Care Med. 2011; 184: 602-615Crossref PubMed Scopus (1794) Google Scholar 6-min walk test according to European Respiratory Society/American Thoracic Society standards,24Holland A.E. Spruit M.A. Troosters T. et al.An official European Respiratory Society/American Thoracic Society technical standard: field walking tests in chronic respiratory disease.Eur Respir J. 2014; 44: 1428-1446Crossref PubMed Scopus (1229) Google Scholar and accelerometery (e-Appendix 1). The CWP consisted of three phases: TDR (0-12 weeks), food reintroduction (13-18 weeks), and weight loss maintenance (19-52 weeks) and was delivered by experienced dietitians with CWP training (e-Appendix 1). The TDR phase comprised a low-energy liquid diet consisting of 825 to 853 kcal/d (approximately 59% carbohydrate, 13% fat, 26% protein, and 2% fiber) administered via sachets of dried soups and shakes in a variety of flavors made up with water by the participant. The dietitian team reviewed participants at 1 week and then fortnightly. To allow flexibility for participants, acknowledging other commitments or logistical limitations, this phase was extended to 20 weeks if participants did not lose > 15 kg by week 12. Conversely, if a participant’s BMI fell to < 23.0 kg/m2, then food reintroduction was introduced earlier. The food reintroduction phase involved a reducing formula diet and stepwise reintroduction of calorie-controlled meals (with fortnightly dietitian review continuing). Flexible periods of 2 to 8 weeks were used for this phase based on participant confidence with weight loss management. In the weight loss maintenance phase, dietitians provided individually tailored calorie prescription for weight stabilization and to prevent weight regain, with monthly reviews. All program phases were underpinned by recognized behavior change strategies.25Leslie W.S. Ford I. Sattar N. et al.The Diabetes Remission Clinical Trial (DiRECT): protocol for a cluster randomised trial.BMC Fam Pract. 2016; 17: 20Crossref Scopus (60) Google Scholar,26McCombie L. Brosnahan N. Ross H. et al.Filling the intervention gap: service evaluation of an intensive nonsurgical weight management programme for severe and complex obesity.J Hum Nutr Diet. 2019; 32: 329-337Crossref PubMed Scopus (25) Google Scholar Dietitian-led relapse treatments to correct weight regain were available.27Brosnahan N. Leslie W. McCombie L. et al.Brief formula low-energy-diet for relapse management during weight loss maintenance in the Diabetes Remission Clinical Trial (DiRECT).J Hum Nutr Diet. 2021; 34: 472-479Crossref Scopus (4) Google Scholar Standard asthma care was continued in all participants in all groups. This included continuation of previously initiated asthma medication, but also modification of asthma treatment based on clinical need; those with worsening asthma received treatment escalation, whereas those with improving disease or lack of treatment efficacy underwent medication removal. All participants continued to be reviewed at their original secondary asthma clinic as part of UC. All participants had the opportunity for weight management advice (ie, healthy eating and promoting exercise if in the UC group), inhaler technique, and asthma education as needed at each study visit. The primary outcome was difference in change in ACQ6 score from baseline (visit 1) to 16 weeks (visit 2) between the CWP and UC groups. Secondary measures included difference in change in AQLQ score from baseline to 16 weeks between CWP and UC groups, overall and in each AQLQ domain (symptoms, activity, emotional, and environmental), and the difference in proportion of participants with ≥ 0.5 change (MCID in ACQ620Juniper E.F. Byrne P.M. Guyatt G.H. et al.Development and validation of a questionnaire to measure asthma control.Eur Respir J. 1999; 14: 902Crossref PubMed Scopus (1813) Google Scholar and AQLQ21Juniper E.F. Guyatt G.H. Willan A. et al.Determining a minimal important change in a disease-specific Quality of Life Questionnaire.J Clin Epidemiol. 1994; 47: 81-87Abstract Full Text PDF PubMed Scopus (1549) Google Scholar) between groups at 16 weeks. For other outcomes, see e-Appendix 1. To demonstrate a difference of 0.5 between mean changes in ACQ6 score in CWP and UC groups from baseline to 16 weeks, based on an SD of 0.5 from a similar population,28Scott H.A. Gibson P.G. Garg M.L. et al.Dietary restriction and exercise improve airway inflammation and clinical outcomes in overweight and obese asthma: a randomized trial.Clin Exp Allergy. 2013; 43: 36-49Crossref PubMed Scopus (187) Google Scholar a sample size of 30 (15 per group) was required, assuming an α values of 0.05, a β values of 0.2, and power of 0.8. A target of 40 participants was chosen to allow for a 25% dropout rate. Participants attending visits 1 and 2 were included for intention-to-treat analysis. Continuous variables were described as mean (95% CI) or median (interquartile range [IQR]) based on distribution and compared using independent t tests or Mann-Whitney U tests, respectively. Change in continuous variables over time was analyzed using the analysis of covariance with the baseline variable as a covariate and comparing change in variables using t tests or Mann-Whitney U tests, depending on distribution. Categorical variables were described as number (percentage) and were compared using Pearson χ 2Global Burden of Disease 2015 Chronic Respiratory Disease CollaboratorsGlobal, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015.Lancet Respir Med. 2017; 5: 691-706Abstract Full Text Full Text PDF PubMed Scopus (1361) Google Scholar test or the Fisher exact test as appropriate. Analyses were performed using IBM SPSS Statistics for Mac version 28 (IBM Corp.); graphs were produced using GraphPad Prism for Mac version 9.3.1 (GraphPad Software). A P value of ≤ .05 was significant. All data analysis was performed by the clinical research fellow using anonymized data. Participants were recruited from August 2019 through August 2021, with 2-year follow-up scheduled to finish in August 2023. Sixteen-week follow-up visits continued until December 2021. Of 36 participants screened, one was ineligible (e-Appendix 1) and 35 were randomized. Two patients were lost to follow-up and 33 patients attended visit 2 to be included in the intention-to-treat analysis (n = 17 in the CWP group, n = 16 in the UC group). Recruitment was halted before the target of 40 because of a lower than expected dropout rate. Overall, mean age was 53 years, 63% were women, 54% were former smokers, and 43% were never smokers. Comorbidities were common, including atopy (71%), allergic (54%) and perennial (46%) rhinitis, gastro-oesophageal reflux disease (86%), mental health problems (51%), and osteopenia or osteoporosis (43%). Significant treatment burden was observed, notably with 17% taking maintenance prednisolone and just over one-third receiving biologic treatment. The study population consisted of those with frequent exacerbations with uncontrolled disease as reflected by the median for oral corticosteroid courses in the previous 12 months of 3 (IQR, 2-5) and mean ACQ6 score of 2.8 (IQR, 2.4-3.1). Mean overall AQLQ score was 3.8 (IQR, 3.4-4.2). Median weight was 101.7 kg (IQR, 91.4-118.7 kg), with a median BMI of 37.5 kg/m2 (IQR, 35.0-42.3 kg/m2), mean waist to hip ratio of 0.99 and mean waist to height ratio of 0.74, all suggestive of a morbidly obese, high-risk population. Low median Feno and eosinophil count (18 ppb and 0.11 × 109/L, respectively) suggested predominance of a T2-low endotype within the population (Fig 1, Table 1, e-Table 1).Table 1Baseline CharacteristicsVariableOverall (n = 35)CWP (n = 18)UC (n = 17)Age, y52.6 (48.3-56.9)56.7 (51.3-62.1)48.3 (41.5-55.1)Female sex22 (62.9)13 (72.2)9 (52.9)Smoking status Current smoker1 (2.9)0 (0.0)1 (5.9) Former smoker19 (54.3)12 (66.7)7 (41.2) Lifelong nonsmoker15 (42.9)6 (33.3)9 (52.9)Smoking, pack-years15.0 (6.0-30.0)15.0 (5.0-22.5)5.0 (0.0-20.0)Age at asthma diagnosis, y30.9 (23.8-38.1)34.3 (24.1-44.4)27.4 (16.6-38.2)Duration of asthma, y21.7 (16.5-27.0)22.5 (13.7-31.3)20.9 (14.3-27.5)Atopy25 (71.4)12 (66.7)13 (76.5)Allergic rhinitis19 (54.3)9 (50.0)10 (58.8)Perennial rhinitis16 (45.7)7 (38.9)9 (52.9)Nasal polyps4 (11.4)3 (16.7)1 (5.9)Nasal surgery4 (11.4)3 (16.7)1 (5.9)Eczema13 (37.1)6 (33.3)7 (41.2)GERD30 (85.7)16 (88.9)14 (82.4)ILO/DFB8 (22.9)5 (27.8)3 (17.6)Psychological illness18 (51.4)8 (44.4)10 (58.8)Emphysema5 (14.3)3 (16.7)2 (11.8)Bronchiectasis1 (2.9)1 (5.6)0 (0.0)SAFS/ABPA9 (25.7)3 (16.7)6 (35.3)Diabetes mellitus4 (11.4)4 (22.2)0 (0.0)Hypertension9 (25.7)6 (33.3)3 (17.6)Cardiac disease7 (20.0)2 (11.1)5 (29.4)Osteopenia/osteoporosis15 (42.9)6 (33.3)9 (52.9)BDP equivalent dose, μg1,600 (1,600-2,000)1,600 (1600-1,600)2,000 (1,600-2,400)LAMA33 (94.3)18 (100.0)15 (88.2)Maintenance prednisolone6 (17.1)4 (22.2)2 (11.8)Prednisolone dose, mg4.5 (1.2-7.8)4.5 (–1.9 to 10.9)4.5 (–1.9 to 10.9)Montelukast27 (77.1)14 (77.8)13 (76.5)Theophylline22 (62.9)10 (55.6)12 (70.6)Azithromycin7 (20.0)6 (33.3)1 (5.9)Omalizumab4 (11.4)1 (5.6)3 (17.6)Mepolizumab8 (22.9)4 (22.2)4 (23.5)Antihistamine24 (68.6)11 (61.1)13 (76.5)Nasal steroid24 (68.6)12 (66.7)12 (70.6)PPI/H2A30 (85.7)17 (94.4)13 (76.5)Previous 12 mo Prednisolone courses3 (2-5)4 (2-5)3 (2-5) Out-of-hours GP visit0 (0-0)0 (0-0)0 (0-0) ED visit0 (0-0)0 (0-0)0 (0-0) Hospital admissions0 (0-1)0 (0-0)0 (0-1) ICU admissions0 (0-0)0 (0-0)0 (0-0)Weight, kg101.7 (91.4-118.7)103.3 (96.9-118.3)97.0 (86.5-122.0)BMI, kg/m237.5 (35.0-42.3)38.2 (35.6-45.3)36.1 (32.7-42.5)MRC dyspnea scale score3 (3-4)3 (3-4)3 (3-4)ACQ6 score2.8 (2.4-3.1)2.8 (2.2-3.3)2.8 (2.2-3.3)AQLQ score Overall3.8 (3.4-4.2)3.8 (3.3-4.4)3.8 (3.2-4.4) Symptom domain3.8 (3.4-4.2)3.7 (3.2-4.3)3.8 (3.2-4.5) Activity domain3.8 (3.4-4.2)3.9 (3.4-4.4)3.7 (3.0-4.3) Emotional domain3.8 (3.2-4.3)3.6 (2.8-4.5)3.9 (3.1-4.7) Environmental domain4.1 (3.6-4.6)4.0 (3.4-4.6)4.2 (3.4-5.0)HAD score Anxiety scale8 (6-11)9 (7-11)7 (5-11) Depression scale8 (5-11)8 (5-11)9 (7-14)Eosinophils, × 109/L0.11 (0.08-0.42)0.17 (0.08-0.42)0.1 (0.04-0.51)Feno, ppb18 (11-33)15 (10-35)20 (13-51)PEF, L/min375 (334-415)318 (275-360)435 (374-496)Spirometry, % FEV1 before BD administration72.1 (66.0-78.1)65.8 (57.1-74.6)78.7 (70.7-86.7) FEV1 to FVC ratio before BD administration70.4 (67.2-73.5)67.9 (62.5-73.2)73.0 (69.7-76.2) FEV1 change after BD administration3.4 (1.3-5.4)5.1 (1.5-8.7)1.5 (-0.5, 3.6)6MWD, m326 (284-367)315 (250-381)337 (282-393)Data are presented as No. (%), mean (95% CI) if parametric, or median (interquartile range) if nonparametric. 6MWD = 6-min walk distance; ABPA = Allergic Bronchopulmonary Aspergillosis; ACQ6 = Asthma Control Questionnaire 6; AQLQ = Asthma Quality of Life Questionnaire; BD = bronchodilator; BDP = beclomethasone dipropionate; CWP = Counterweight-Plus Programme; DFB = dysfunctional breathing; Feno = fractional exhaled nitric oxide; GERD = gastroesophageal reflux disease; GP = general practitioner; HAD = Hospital Anxiety and Depression; H2A = H2-receptor antagonist; ILO = inducible laryngeal obstruction; LAMA = long-acting antimuscarinic; LPA = low physical activity; MRC = Medical Research Council; MVPA = moderate to vigorous physical activity; PEF = peak expiratory flow; ppb = parts per billion; PPI = proton pump inhibitor; SAFS = severe asthma with fungal sensitization; UC = usual care. Open table in a new tab Data are presented as No. (%), mean (95% CI) if parametric, or median (interquartile range) if nonparametric. 6MWD = 6-min walk distance; ABPA = Allergic Bronchopulmonary Aspergillosis; ACQ6 = Asthma Control Questionnaire 6; AQLQ = Asthma Quality of Life Questionnaire; BD = bronchodilator; BDP = beclomethasone dipropionate; CWP = Counterweight-Plus Programme; DFB = dysfunctional breathing; Feno = fractional exhaled nitric oxide; GERD = gastroesophageal reflux disease; GP = general practitioner; HAD = Hospital Anxiety and Depression; H2A = H2-receptor antagonist; ILO = inducible laryngeal obstruction; LAMA = long-acting antimuscarinic; LPA = low physical activity; MRC = Medical Research Council; MVPA = moderate to vigorous physical activity; PEF = peak expiratory flow; ppb = parts per billion; PPI = proton pump inhibitor; SAFS = severe asthma with fungal sensitization; UC = usual care. Individuals in the CWP group were slightly older, had lower baseline peak expiratory flow rate and FEV1, and were more sedentary, with accelerometery data demonstrating more inactive time and less time spent in light to moderate vigorous physical activity compared with the UC group. No other between-group differences were observed. Over 16 weeks, mean change in ACQ6 score was –0.45 (IQR, –1.02 to 0.13) for the CWP group and 0.23 (IQR, –0.17 to 0.63) for the UC group, with a mean difference of –0.69 (IQR, –1.37 to –0.01; P = .048) between groups (Table 2, e-Table 2, Fig 2).Table 2Intention-to-Treat Comparison of Asthma Control and Quality-of-Life Outcomes Between CWP and UC Groups Over 16 WeeksVariableCWP Group (n = 17)UC Group (n = 16)Mean Difference Between CWP and UC GroupsP ValueaComparison of mean difference using analysis of covariance with baseline variable as covariate.ACQ6–0.45 (–1.02 to 0.13)0.23 (–0.17 to 0.63)–0.69 (–1.37 to –0.01).048AQLQ Overall0.81 (0.28-1.35)0.08 (–0.32 to 0.48)0.76 (0.18-1.34).013 Symptom domain0.98 (0.44-1.52)0.25 (–0.13 to 0.63)0.72 (0.14-1.31).018 Activity domain0.53 (0.01-1.05)–0.13 (–0.73 to 0.46)0.78 (0.08-1.47).029 Emotional domain1.47 (0.59-2.35)0.66 (0.07-1.25)0.72 (–0.16 to 1.59)0.104 Environmental domain0.52 (–0.26 to 1.30)–0.52 (–1.30 to 0.26)0.98 (0.01-1.96).048Data are presented as mean (95% CI), unless otherwise indicated. ACQ6 = Asthma Control Questionnaire 6; AQLQ = Asthma Quality of Life Questionnaire; CWP = Counterweight-Plus Programme; UC = usual care.a Comparison of mean difference using analysis of covariance with baseline variable as covariate. Open table in a new tab Data are presented as mean (95% CI), unless otherwise indicated. ACQ6 = Asthma Control Questionnaire 6; AQLQ = Asthma Quality of Life Questionnaire; CWP = Counterweight-Plus Programme; UC = usual care. Over 16 weeks, mean change in overa